Pathway · 4 proteins
Coenzyme A
Assemble the carrier used in acyl-group transfer.
How it works
- Pantothenate is phosphorylated by a type III pantothenate kinase, then coupled to cysteine by CoaBC, a bifunctional ligase/decarboxylase in VF5, producing the pantetheine arm.
- Pantetheine-phosphate adenylyltransferase attaches AMP to give dephospho-CoA, and dephospho-CoA kinase phosphorylates the 3'-hydroxyl to complete coenzyme A.
- CoA is the carrier for the acetyl, succinyl and malonyl groups used throughout central carbon and lipid metabolism. This module builds the carrier; the reactions that load and unload it are described in those systems.
Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.
Its proteins
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Type III pantothenate kinase | 2.7.1.33 | (R)-pantothenate + ATP = (R)-4'-phosphopantothenate + ADP + H(+) | K(+) | 229 | Step named |
| Dephospho-CoA kinase | 2.7.1.24 | 3'-dephospho-CoA + ATP = ADP + CoA + H(+) | — | 196 | Step named |
| Phosphopantetheine adenylyltransferase | 2.7.7.3 | (R)-4'-phosphopantetheine + ATP + H(+) = 3'-dephospho-CoA + diphosphate | Mg(2+) | 161 | Step named |
| Coenzyme A biosynthesis bifunctional protein CoaBC | 4.1.1.36; 6.3.2.5 | (R)-4'-phosphopantothenate + L-cysteine + CTP = N-[(R)-4-phosphopantothenoyl]-L-cysteine + CMP + diphosphate + H(+) | FMN, Mg(2+) | 388 | Step named |
Origins
Could coenzyme A, the carrier of acetyl and acyl groups, have formed before cells?
Miller and colleagues reported prebiotic syntheses of pantoic acid and pantothenic acid (1993) and a possible prebiotic synthesis of pantetheine (Keefe, Newton and Miller, Nature 1995), all parts of coenzyme A. Pantetheine also appears in some abiotic reactions.
The parts still have to be joined to an adenine nucleotide to make the whole cofactor, and the books report no prebiotic route to that.
In the cell, acetyl-CoA forms through an activated intermediate that the enzyme shields from water, and the energy is drawn from ATP.
From the books: Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, pp. 67 and 74; Horton et al., Principles of Biochemistry, p. 371.
The wider question for this part of the cell: origins for manufacturing cofactors and vitamins.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: Heme and quinones · Biotin and lipoate · NAD and flavins · Thiamine and pyridoxal · Folate and pterin chemistry · Lipid and cofactor connections · Aspartate-family branches · Amino-acid connections · Folate-linked carbon transfer · Serine, glycine and sulfur · Folate biosynthesis · Oxidative phosphorylation · Thiamine metabolism · Pantothenate and CoA biosynthesis · Glycine, serine and threonine metabolism · Riboflavin metabolism · Nicotinate and nicotinamide metabolism · Biotin metabolism · Cysteine and methionine metabolism · Porphyrin metabolism · Pyruvate metabolism · Not yet placed in a pathway